<p><b><i>Background:</i></b> Mild to moderate depressive symptoms are common but often remain unrecognized and treated inadequately. We hypothesized that an Internet intervention in addition to usual care is superior to care as usual alone (CAU) in the treatment of mild to moderate depressive symptoms in adults. <b><i>Methods:</i></b> This trial was controlled, randomized and assessor-blinded. Participants with mild to moderate depressive symptoms (Patient Health Questionnaire, PHQ-9, score 5-14) were recruited from clinical and non-clinical settings and randomized to either CAU or a 12-week Internet intervention (Deprexis) adjunctive to usual care. Outcomes were assessed at baseline, 3 months (post-assessment) and 6 months (follow-up). The primary outcome measure was self-rated depression severity (PHQ-9). The main analysis was based on the intention-to-treat principle and used linear mixed models. <b><i>Results:</i></b> A total of 1,013 participants were randomized. Changes in PHQ-9 from baseline differed signiﬁcantly between groups (t<sub>825</sub> = 6.12, p < 0.001 for the main effect of group). The post-assessment between-group effect size in favour of the intervention was <i>d</i> = 0.39 (95% CI: 0.13-0.64). It was stable at follow-up, with <i>d</i> = 0.32 (95% CI: 0.06-0.69). The rate of participants experiencing at least minimally clinically important PHQ-9 change at the post-assessment was higher in the intervention group (35.6 vs. 20.2%) with a number needed to treat of 7 (95% CI: 5-10). <b><i>Conclusions:</i></b> The Internet intervention examined in this trial was superior to CAU alone in reducing mild to moderate depressive symptoms. The magnitude of the effect is clinically important and has public health implications.</p><br>